López-Sánchez, MacarenaLoucera, CarlosPeña-Chilet, MaríaDopazo, Joaquín2023-05-032023-05-032022http://hdl.handle.net/10668/19784Recent studies have demonstrated a relevant role of the host genetics in the coronavirus disease 2019 (COVID-19) prognosis. Most of the 7000 rare diseases described to date have a genetic component, typically highly penetrant. However, this vast spectrum of genetic variability remains yet unexplored with respect to possible interactions with COVID-19. Here, a mathematical mechanistic model of the COVID-19 molecular disease mechanism has been used to detect potential interactions between rare disease genes and the COVID-19 infection process and downstream consequences. Out of the 2518 disease genes analyzed, causative of 3854 rare diseases, a total of 254 genes have a direct effect on the COVID-19 molecular disease mechanism and 207 have an indirect effect revealed by a significant strong correlation. This remarkable potential of interaction occurs for >300 rare diseases. Mechanistic modeling of COVID-19 disease map has allowed a holistic systematic analysis of the potential interactions between the loss of function in known rare disease genes and the pathological consequences of COVID-19 infection. The results identify links between disease genes and COVID-19 hallmarks and demonstrate the usefulness of the proposed approach for future preventive measures in some rare diseases.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/COVID-19HumansModels, StatisticalRare DiseasesVirus Diseasesresearch article35022696open access10.1093/hmg/ddac0071460-2083PMC9239744https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddac007/42366554/ddac007.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239744/pdf